Resveratrol protects against methotrexate-induced hepatic injury in rats. 2010

Tugba Tunali-Akbay, and Ozer Sehirli, and Feriha Ercan, and Goksel Sener
Marmara University School of Dentistry, Department of Biochemistry, Istanbul, Turkey. ttunali@marmara.edu.tr

OBJECTIVE The aim of this study to investigate the possible protective effect of resveratrol on some liver and serum/plasma parameters in methotrexate induced toxicity in rats. Methotrexate is used widely to treat various neoplastic diseases such as acute lymphoblastic leukemia, lymphoma, solid cancers, and autoimmune diseases. We hypothesized that resveratrol has a potential to decrease the oxidant damage in MTX-induced hepatic injury. METHODS Following a single dose of methotrexate (20 mg/kg, i.p.), either saline or resveratrol (10 mg/kg, orally) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the liver was removed to measure malondialdehyde and glutathione levels, myeloperoxidase and thromboplastic activities and collagen content. Aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase activity were measured in the serum samples, while TNF-alpha and total antioxidant capacity were assayed in plasma samples. RESULTS Our results showed that MTX administration increased the hepatic malondialdehyde levels, myeloperoxidase and thromboplastic activities and collagen contents and decreased glutathione, while these alterations were reversed in resveratrol-treated group. Elevated aspartate aminotransferase and alanine aminotransferase activities and TNF-alpha level observed following MTX treatment was depressed with resveratrol. CONCLUSIONS The present study showed that resveratrol protects against methotrexate-induced hepatic injury and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D005260 Female Females
D000077185 Resveratrol A stilbene and non-flavonoid polyphenol produced by various plants including grapes and blueberries. It has anti-oxidant, anti-inflammatory, cardioprotective, anti-mutagenic, and anti-carcinogenic properties. It also inhibits platelet aggregation and the activity of several DNA HELICASES in vitro. 3,4',5-Stilbenetriol,3,4',5-Trihydroxystilbene,3,5,4'-Trihydroxystilbene,Resveratrol, (Z)-,Resveratrol-3-sulfate,SRT 501,SRT-501,SRT501,cis-Resveratrol,trans-Resveratrol,trans-Resveratrol-3-O-sulfate,Resveratrol 3 sulfate,cis Resveratrol,trans Resveratrol,trans Resveratrol 3 O sulfate
D000410 Alanine Transaminase An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. Alanine Aminotransferase,Glutamic-Pyruvic Transaminase,SGPT,Alanine-2-Oxoglutarate Aminotransferase,Glutamic-Alanine Transaminase,Alanine 2 Oxoglutarate Aminotransferase,Aminotransferase, Alanine,Aminotransferase, Alanine-2-Oxoglutarate,Glutamic Alanine Transaminase,Glutamic Pyruvic Transaminase,Transaminase, Alanine,Transaminase, Glutamic-Alanine,Transaminase, Glutamic-Pyruvic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000964 Antimetabolites, Antineoplastic Antimetabolites that are useful in cancer chemotherapy. Antineoplastic Antimetabolites
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D001219 Aspartate Aminotransferases Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1. Aspartate Aminotransferase,Aspartate Transaminase,Glutamic-Oxaloacetic Transaminase,SGOT,Aspartate Apoaminotransferase,Glutamate-Aspartate Transaminase,L-Aspartate-2-Oxoglutarate Aminotransferase,Serum Glutamic-Oxaloacetic Transaminase,Aminotransferase, Aspartate,Aminotransferase, L-Aspartate-2-Oxoglutarate,Aminotransferases, Aspartate,Apoaminotransferase, Aspartate,Glutamate Aspartate Transaminase,Glutamic Oxaloacetic Transaminase,Glutamic-Oxaloacetic Transaminase, Serum,L Aspartate 2 Oxoglutarate Aminotransferase,Serum Glutamic Oxaloacetic Transaminase,Transaminase, Aspartate,Transaminase, Glutamate-Aspartate,Transaminase, Glutamic-Oxaloacetic,Transaminase, Serum Glutamic-Oxaloacetic

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